Overactive bladder (“OAB”) is a term for a syndrome that encompasses urge incontinence, urgency and frequency. Urinary incontinence (“UI”) is the involuntary loss of urine that results from an inability of the bladder to retain urine as a consequence of either urge (urge incontinence), or physical or mental stress (stress incontinence).
The normal bladder fills at a physiological rate dictated by the function of the kidneys. The bladder can accommodate large volumes of urine due to the physical properties of the bladder as well as a neural inhibitory system. The inhibitory mechanism is believed to involve inhibition of parasympathetic activity or an increase in sympathetic tone to produce detrusor relaxation and allow filling to occur. During filling the outlet neck of the bladder and urethra are contracted preventing leakage. Voiding or micturition is characterized by a relaxation of the outlet neck and the urethra followed by contraction of the detrusor muscle. When the bladder is empty the detrusor muscle relaxes and the outlet neck and urethra contract to seal off the bladder and maintain continence.
Between 4 and 8% of the total population are estimated to suffer from UI at any point in time, although in most countries, only about 15% of such sufferers are diagnosed. Of those diagnosed only about 70% receive medical treatment. Urge incontinence is more prevalent in the elderly and 80% of the cases are female. Pads and other physical devices are regularly used by a large proportion of incontinent patients not receiving medical treatment. The US market for incontinence pads was estimated at $1.5 billion in 1997.
The muscarinic antagonist oxybutin is prescribed for treatment for OAB in western countries and a second generation muscarinic M3 receptor antagonist, tolterodine, is also marketed for OAB. Propiverine and Flavoxate are prescribed in Japan. Estrogen and progesterone therapy has been studied and is believed to partially alleviate incontinence in some women. Other studies suggest alpha-adrenergic agonists, beta-adrenergic-receptor blocking agents cholinergic receptor-blocking compounds and cholinergic receptor-stimulating drugs may be beneficial. However, existing therapies are associated with side effects including constipation, visual-accommodation abnormalities, xerothalmia (dry eyes) and a “dry mouth” side effect, which is poorly tolerated by some users and therefore, despite the availability of existing treatments, there is a major unmet and growing need for an effective and acceptable medical treatment for UI and OAB.